Hydrogel microbeads having a secondary layer

ABSTRACT

A microbead having a matrix core comprising a hydrophilic matrix and droplets of active material entrained therein, and a secondary layer adjacent to the outer surface of the matrix core. The secondary layer may be ionically complexed or hydrogen bonded to the matrix core surface. Compositions comprising the microbeads suspended in solution may be sprayable. The microbeads of the invention may be controllable by exposing the microbeads to high or low humidity or moisture.

FIELD OF THE INVENTION

[0001] The invention relates broadly to immobilization and release ofactive material within hydrogel microbeads having a secondary layer. Thehydrogel microbeads can be used to immobilize water soluble and waterinsoluble actives such as oils, fragrances, lubricants, and agriculturalchemicals such as pheromones, herbicides, insecticides and pesticides.

BACKGROUND

[0002] Methods of eliminating unwanted pests from orchards, crops andforests frequently entail the use of organophosphate insecticides.Alternative methods involve insect mating disruption, where insectpheromones are used to control pests and protect agricultural crop. Ininsect mating disruption methods, the mating pheromone plume of a femaleinsect is typically masked with other pheromone point sources. Thisreduces the likelihood of a male insect finding a female, andsubsequently disrupts and reduces larvae production. The insectpopulation of the next generation is thus decreased, as well aspotential crop damage.

[0003] Conventional sprayable pheromone formulations are generallyprovided in liquid filled microcapsules containing an active. Typically,the microcapsules have a polyurea membrane that can be formed using aninterfacial process involving an isocyanate and an amine.Microencapsulation by this method has been described for example in U.S.Pat. No.4,487,759 (Nesbitt et al., 1984). These polyurea membranes allowactives to be released into the atmosphere for up to a total of 2-3weeks for most insect pheromones.

[0004] Use of interfacial condensation to encapsulate substances such aspharmaceuticals, pesticides and herbicides is taught in U.S. Pat. No.3,577,515. The encapsulation process involves two immiscible liquidphases (typically water and an organic solvent), one being dispersed inthe other by agitation, and the subsequent polymerization of monomersfrom each phase at the interface between the bulk (continuous) phase,and the dispersed droplets. Polyurethanes and polyureas are materialssuitable for producing the microcapsules. The microcapsules comprise apolymeric sphere and a liquid centre, ranging from 30 micron to 2 mm indiameter, depending on monomers and solvents used.

[0005] Highly viscous and thickened hydrogels have been used to deliverpheromones, fragrances and other non-water soluble actives. U.S. Pat.No. 4,755,377, for example, describes a process of encapsulating perfumeor fragrant material within an aqueous-based gel composition. Theresulting material is in the form of a highly viscous semi-solid. U.S.Pat. No. 5,645,844 describes the use of chitosan paste for delivery ofpheromones to disrupt insect mating, where the material can be dispensedby an apparatus such as a caulking gun. Due to their thickness and highviscosity, these materials, however, are generally unsprayablecompositions.

[0006] Most hydrogels are safe and non-toxic to humans. Hydrogels arehave been used for the encapsulation of biological materials whereby theformulation is non-lethal to the viability of the cells, proteins, andrelated materials. U.S. Pat. No. 4,689,293, describes the process ofencapsulating living tissue or cells in alginate beads. Theencapsulation shell permits the passage of materials and oxygen to thecells and permits the diffusion of the metabolic by-products from thegel. In U.S. Pat. No. 5,635,609, the encapsulation art describedinvolves one esterified polysaccharide (i.e., alginate) and onepolyamine (i.e. chitosan) whereby the outer surface membranes are formedthrough covalent amide bonds. U.S. Pat. No. 4,439,488 teaches a processof encapsulating pheromone whereby the biological agents are dissolvedor dispersed in an aqueous paste of a gel-forming polyhydroxy polymer.By adding boric acid to an alkaline pH, the paste transforms into a gelthereby entrapping the agents in a protective matrix.

[0007] Japanese patent S 60-252403 describes a method of formingsprayable, slow release pheromone agent obtained by emulsificationco-polymerization. In Japanese patent H-9-1244-08, the outer surface ofthe delivery system (i.e., synthetic resin or inorganic substance) iscoated by a water-proof material. The water-proof agent can be asilicon, fluroine, or paraffin hydrogen carbide type material.

SUMMARY OF THE INVENTION

[0008] A method of delivering active material using a plurality ofmicrobeads suspended in solution is provided, where the microbeadscomprise a hydrophilic matrix having droplets of active materialentrained therein and a secondary layer adjacent to the surface of thematrix. Furthermore, the matrix is capable of immobilizing a broadspectrum of active materials, either water soluble or non-water soluble.In one aspect of the invention, the hydrophilic matrix may be made froma naturally occurring material to provide an environmentally friendlymicrobead.

[0009] In an aspect of the invention, the active entrained in the matrixdiffuses through the hydrophilic matrix and the secondary layer, and isreleased into the environment over an extended period.

[0010] In another aspect, the microbeads are capable of re-hydratingafter an initial dehydration and release of active. Thus, the releaseand longevity of the active can be controlled by adjusting the humidityof the environment in which the microbeads have been delivered.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011]FIG. 1 is a cross-sectional illustration depicting a preferredembodiment of a microbead of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] In view of the increasing awareness of insecticide toxicity tohumans and other environmental concerns, it would be advantageous toprovide an active delivery system having an extended release life andhaving a hydrogel material in order that it be non-toxic andbio-degradeable. It would also be advantageous to provide a system forsprayable long lasting active delivery that would be applicable to abroad spectrum of actives thereby eliminating the issue of reactivity ofthe active with one of the membrane components.

[0013] The present invention provides microbeads having a secondarylayer, where the microbeads are made of a hydrophilic matrix core havingdroplets of active material entrained and immobilized therein.Surprisingly, it has been found that release of the active from withinthe microbeads can be altered by adding a secondary layer onto themicrobead surface to alter the diffusion pathway of the active andsubsequently extend and improve the active release properties.Furthermore, the secondary layer advantageously provides physicalprotection to the hydrogel matrix with the active entrained therein,from rupturing forces, UV, and other external environmental conditions.

[0014] The secondary layer can be a membrane, web, coating, film, orother material that is positioned outside and adjacent to the outersurface of the matrix core. For simplicity, the term “secondary” layeris used herein to describe the layer that lays immediately outside thesurface of the matrix core. Thus, it is contemplated, that themicrobeads of the invention can have multiple layers.

[0015] The microbeads of the invention comprise a matrix formingmaterial, and is preferably substantially spherical. The matrix formingmaterials of the microbead core are hydrophilic and water soluble.Entrained or finely dispersed within the matrix are micro-sized dropletsof active material. Active materials that can be immobilized within thehydrogel microbeads include acetates, aldehydes, alcohols, esters, epoxycompounds, ethers, and ketones, especially reactive ketones in which thedouble bond of the carbonyl group is conjugated with one or more doublebonds, for example acetophenone where the carbonyl group is conjugatedwith double bonds of the aromatic ring.

[0016] Advantageously, the hydrogel matrix core is preferably made fromenvironmentally or biologically friendly materials to provide sufficientimmobilization of oil soluble actives such that the active can bedelivered and sprayed by conventional techniques. By utilizing ahydrophilic matrix core, the hydrogel microbeads entrap micro-sizeddroplets of active material within the matrix. This is in contrast todelivery systems that solely utilize microencapsulation of actives,achieved by interfacial condensation. Immobilizing active material in ahydrophilic matrix core advantageously imparts the capability of thehydrogel microbeads to immobilize oil-soluble active materials andminimizes the risk of undesired reactivity between the active and itsimmobilizer. Thus, immobilization of active materials by use of themicrobeads of the invention does not render the immobilized materialinert or ineffective.

[0017] It has also been surprisingly found that the microbeads of theinvention provide a method of controlling release of active(s) bycyclically hydrating and re-hydrating the microbeads. This is a resultof the surprising benefit from immobilizing active ingredients inhydrogel microbeads, where the microbead is able to “swell” under humidconditions and shrink under dry conditions. As used herein, “swell” isdescriptive of the behavior of a microbead, wherein the size (volume) isenlarged (increased) due to absorption of water. The microbeads' abilityto swell is likely due to the hydrophilic nature of the matrix formingmaterials used to immobilize the active material.

[0018] In the presence of humidity, the hydrogel microbeads aresurprisingly found to be capable of absorbing moisture, rehydrating, andconsequently releasing active material contained within the microbead.This behavior can be cyclical. Thus, by controlling the humidity (ordryness) of the ambient air, the release rate of active material fromthe microbeads can be controlled such that specific periods of releasecan be generally predicted. It is therefore possible with the presentinvention to release the active material on demand from the microbead.Release on demand, or “smart release,” can be advantageous in thoseinstances where release is preferred at certain times. The microbeads'ability to release more active out from the matrix may increase thelongeveity of the release period. Preferably, the microbeads aredelivered to an intended environment in effective amounts to obtain thedesired effect. For example, microbeads having pheromones entrainedtherein, are preferably delivered to a desired area in amounts such thatmating disruption is effected and release is accomplished for more than4 weeks, more preferably, the microbead can release for more than about6 weeks; and most preferably more than about 8 weeks.

[0019] During the drying process (i.e dehydration) a surface film layerwill form as a result of water evaporation from the hydrophilic matrix.Both initially and during use, the microbeads are characterized by alarge surface area to volume ratio, which helps maintain the rate ofdiffusion of the active material during use. Thus, it has been foundthat microbeads made according to the method of present inventionprovide excellent delivery systems as they are capable of releasingactive material for extended periods. Furthermore, since the active isdispersed within a water-based matrix, additional protection fromenvironmental conditions (i.e., UV) can be provided.

[0020] Although it has been found that microbeads of the invention canbe made having a diameter of up to about 5 millimeters (mm), it ispreferred that the microbeads be between about 1 micrometers (μm) toabout 1000 μm and more preferably between about 1 μm to about 500 μm indiameter to ensure that the microbeads are easily sprayable fromconventional spray nozzles. Most preferably, to ensure minimal cloggingin conventional nozzles, the microbeads are less than about 400 μm indiameter. It is contemplated, however, that with the advent of largerspray nozzles not yet realized in the industry, the microbeads can beprovided in much greater diameters.

[0021] For spraying applications, particularly aerial spraying, it isdesirable that the microbeads be capable of remaining suspended insolution (e.g., water) to ensure that the microbeads do not sink,settle, or coagulate in the suspension. A uniform suspension ensures aneven spray coverage. Preferably, the microbeads of the invention areable to remain in suspension, thus minimizing if not eliminating theneed to agitate during application (and storage). Various suspensionaids can also be included in the suspension containing the microbeads ofthe invention. Examples of suitable suspension aids include rhamsam gum,xanthum gum, gellan gum, pectin, and gum arabic.

[0022] Owing to the handling to which the microbeads are subjected, itis desirable that the microbeads of the present invention should besomewhat elastic, and not frangible. For example, typical atomization ofa suspension during a spray application will force the suspensionthrough two rotating perforated discs that are immediately upstream ofthe discharge nozzle. Sufficient elasticity of the microbeads minimizesphysical damage to the microbeads as they pass through the discs.

[0023] The microbeads of the present invention comprise a hydrophilicmatrix core having active material droplets entrained therein, and asecondary layer adjacent matrix forming material and active material.Referring now to FIG. 1, a preferred embodiment is shown, where aplurality of active material droplets 10 is entrained within thehydrogel matrix 12, and a layer 14 adjacent to outer surface 16 of thematrix 12. As seen in FIG. 1, active material droplets are preferablylocated between and within the hydrogel matrix, where the matrixprovides an immobilizing network around the droplets. The degree andextent of agitation as well as the type of surfactant used to form themicrobeads can affect the size and the dispersity of the pheromonedroplets within microbead's matrix. Droplets are preferably betweenabout 0.01 mn to about 200,000 nm in diameter. More preferably, thedroplets are between about 1 to about 1000 nm.

[0024] The matrix-forming material useful in the present invention arebiocompatible, water-soluble, have pendant functional groups, andcomplex with ions (e.g., polyvalent cations and/or anions) to formhydrogels. Functional groups of the matrix forming material include forexample, carboxyls, hydroxyls, primary or secondary amines, aldehydes,ketones, esters, or combinations thereof. Preferably, the matrix-formingmaterial of the hydrophilic matrix core can be made from naturaloccurring polysaccharides, such as alginates, chitosans, gums, agars,carrageenans, or the matrix can be made synthetic, water solublemonomers, oligomers or polymers, such as, for example, polyvinylalcohol, poly(N-isoproylacrylamide), acrylamides, acrylates,methacrylates or combinations thereof.

[0025] Suitable naturally occurring polysaccharides include thewater-soluble salts of alginic, pectic and hyaluronic acids, thewater-soluble salts or esters of polyglucuronic acid, polymanuronicacid, polylygalacturonic acid and polyarabinic acid, and gumkappa-carrageenan. The preferred polysaccharides are the ammonium,magnesium, potassium, sodium and other alkali metal salts of alginicacid, and the most preferred polysaccharide is sodium alginate.

[0026] “Alginate” is the general name given to alginic acid and itssalts. Alginates are composed of D-mannosyluronic (mannuronic - “M”) andL-gulopyranosyluronic (guluronic - “G”) acid residues. The ratio ofmannuronic to guluronic acid residues is known as the M:G ratio. Thealginate used to immoblize active droplets should be carefully selectedto ensure proper microbead formation, ensure the stability of themicrobeads during storage and delivery applications, and ensure that themicrobeads are able to shrink and swell appropriately to deliver thedesired active material over an extended period of time (preferably 4-6weeks). Preferably, an alginate is chosen such that the matrix formed issufficient in strength to withstand the shear forces (conditions) placedupon the microbeads during application via a spray nozzle - i.e., themicrobeads are resistant to rupture during the spray application.

[0027] For strength and stability of the microbeads, it is desirable tochoose a proper molecular weight of the alginate, as well as anappropriate M:G ratio. Although alginates high in mannuronic acid aregenerally useful for thickening applications, whereas alginates with ahigh level of guluronic acid are often used for forming gels, bothalginate categories (individually or a mixture thereof) are suitable forthe microbeads of the invention. A preferred alginate that impartsstrength and rupture resistance is an alginate that has a high level ofguluronic acid, e.g., greater than about 30 percent by weight. Alginatecompositions with excessive levels of mannuronic acid could result inless stable and less rigid microbeads than high guluronic acid gels.However, high mannuronic acid alginates impart to the microbeads thecapability of swelling and absorbing more water than microbeads of highguluronic acid content. Thus, a careful balance of the advantagesimparted by each of M and G residues should be considered when choosinga suitable alginate.

[0028] It has been surprisingly found that alginates preferably having amolecular weight in the range of about 100,000 kg/mol to about 2,500,000kg/mol, more preferably about 200,000 kg/mol to about 1,500,000 kg/mol.Furthermore, the alginates preferably have an M:G ratio in the range ofabout 0.2 to about 3.5; more preferably about 0.3 to about 1.85.

[0029] Suitable alginates that have a high level of guluronic acid, forexample are alginates from the algae Laminaria hyperborea, stem, wholeplant or frond. Preferred alginates with high levels of mannuronic acidinclude Ascophyllum nodosum, for example.

[0030] Gel matrices formed by crosslinking polysaccharides bearingpendant carboxylate groups are also useful in the present invention.These compounds are composed of water-insoluble alginates which include,with the exception of magnesium and the alkali metal salts, the group IImetal salts of alginic acid. The water-insoluble alginate gels aretypically formed by the chemical conversion of water-soluble alginates,in an aqueous solution, into water-insoluble alginates. This conversionusually is accomplished by the reaction of a water-soluble alginate withpolyvalent cations released from a soluble di- or trivalent metal salt.

[0031] Water-soluble alginates can include the ammonium, magnesium,potassium, sodium, and other alkali metal salts of alginic acid.Water-insoluble di-or trivalent metal salts suitable for the presentinvention should satisfy two requirements: (1) that the water-insolublemetal salt contain a di-or trivalent metal ion capable of complexingwith the pendant carboxylate groups of the water-soluble polysaccharideto cause the formation of a water-insoluble polysaccharide gel; and (2)that the water-insoluble metal salt reacts with a water-soluble acid toform a water-soluble metal salt.

[0032] A common and suitable alginate gel is composed of calciumaliginate.

[0033] Sources for the crosslinking calcium ions used in the formationof alginate gels include, for example, calcium carbonate, calciumsulfate, calcium chloride, calcium phosphate, calcium tartrate, calciumnitrate, and calcium hydroxide. Other acceptable crosslinkers mayinclude lanthanum chloride, ferric chloride, cobaltous chloride, asgenerally are other compounds with multivalent cations, such as calcium(Ca++), copper (Cu++), barium (Ba++), strontium (Sr++) and the like.

[0034] The time of gelation of the calcium alginate gels can beaccomplished by regulating the concentration of free calcium ions in thesolution. Typically the concentration of free calcium ions is controlledby manipulation of the ionization rate of the calcium salt and/or by theinclusion of other compounds in the solution which react with the freecalcium ions.

[0035] It has been advantageously found that it is possible toimmobilize and deliver a wide range of active materials, includingnon-water soluble materials as well as alcohols.

[0036] Preferred active materials entrained in the matrix core arepartially water-miscible organic molecules of compounds that have amolecular weight in the range of between about 100 to about 400,preferably between about 150 to 300. The compounds contain a heteroatomthat confers some degree of water-miscibility. For many compounds ofinterest the sole heteroatom is oxygen, and there may be up to threeheteroatoms per molecule in, for instance, hydroxy-substituted orketo-substituted carboxylic acids. Unsubstituted carboxylic acids ofcourse contain two oxygen atoms and simple aldehydes, ketones and etherscontain only one oxygen atom. Compounds that contain nitrogen and/orsulphur atoms are also of interest.

[0037] Of particular interest are biologically active compounds. Forpurposes of the present invention, the term “biologically active” meansmaterials that affect the life processes of organisms. Materials thatare biologically active include herbicides, pesticides, pharmaceuticals,and semiochemicals, including naturally and artificially producedpheromones and synthetic pheromone analogs. Materials of this naturethat are of particular interest are those materials that interfere witha life process essential to the survival of a target pest.

[0038] The method of the invention can be used to immobilize pheromonewith functional groups such as acetates, aldehydes, ketones, alcohols,esters, ethers, epoxies or combinations thereof. Pheromones may bedefined as compounds which, when naturally produced, are secreted by onemember of an animal species which can influence the behaviour ordevelopment of another member of the same animal species. Pheromonesgenerally are species-specific and therefore the application ofpheromones for insect behaviour modification has minimal effect onnon-target pests. Pheromones supplied for modification of insectbehaviour interfere with the “mate finding process” by releasing pointsources of pheromone, which may compete with or camouflage the pheromoneplume of a female. This latter type of action differs from chemicalinsecticides or insect growth regulators or hormones, in that pheromonestarget future generations of insects, not present ones. As pheromonesare very species-specific and are used only in small quantities, theiruse is more environmentally acceptable than broadcasting of pesticides.

[0039] Many pheromones have an ester terminal group, for example andacetate or formate group. Typically these substances arewater-immiscible and incorporation of them into microcapsules by knownmethods presents no particular problem. Many other pheromones have analdehyde or an alcohol terminal group. In general, these are partiallywater-miscible and potentially reactive with the reactants used toencapsulate by prior, conventional methods. In particular, it isdifficult to achieve high degrees of encapsulation of materials thathave some degree of water solubility, as the material partitions betweenthe small amount of organic solvent and the relatively larger amount ofwater that constitutes the continuous phase. Furthermore, thesecompounds can be expected to react with the reactants used toencapsulate. Aldehydes and ketones react with amines to form aldiminesand ketimines, respectively. Alcohols, carboxylic acids and mercaptansreact with isocyanates. Epoxy compounds react both with amines and withisocyanates. Thus, the present invention overcomes the limitation ofdelivering partially water-miscible substances such as alcohols,aldehydes, carboxylic acids, ketones, ethers, including epoxy compounds,and mercaptans.

[0040] Pheromones useful in the inventive microbeads are preferablyinsect pheromones. In describing the structure of the a pheromone, thefollowing notation is used: the type (E (trans)or Z(cis)) and positionof the double bond or bonds are given first, the number of carbon atomsin the chain is given next and the nature of the end group is givenlast. To illustrate, the pheromone Z-10 C19 aldehyde has the structure;

[0041] Pheromones can be mixtures of compounds with one component of themixture predominating, or at least being a significant component.Partially water-miscible significant or predominant components of insectpheromones, with the target species in brackets, include, for example:E/Z-11 C14 aldehyde (Eastern Spruce Budworm), Z-10 C19 aldehyde (YellowHeaded Spruce Sawfly), Z-l 1 C14 alcohol (Oblique Banded Leafroller),Z-8 C12 alcohol (Oriental Fruit moth) and E,E-8,10 C12 alcohol (Codlingmoth), E-1 1 C14 acetate (Sparganothis Fruitworm), and Z-11 C14 acetate(Blackheaded Fireworm).

[0042] An example of a ketone that is a pheromone is E or Z7-tetradecen-2-one, which is effective with the oriental beetle. Anether that is not a pheromone but is of value is 4-allylanisole, whichcan be used to render pine trees unattractive to the Southern pinebeetle.

[0043] Preferred embodiments of the invention are described withreference to immobilization of partially water-miscible and waterimmiscible pheromones, but it should be appreciated that the inventionextends to immobilization of materials other than such pheromones and tomicrobeads containing materials other than pheromones. Those materialsmay, or may not, be biologically active.

[0044] For example, alternatively, active materials containingmercaptans can be immobilized in the microbeads of the invention, suchas what is found in urine of animals. These compounds are preferable insituations where animals mark their territory by means of urine, todiscourage other animals from entering the particular territory.Examples of such animals include preying animals such as wolves, lions,dogs, etc. By dispersing hydrogel microbeads containing the appropriatemercaptans, it is possible to define a territory and discourageparticular animals from entering that territory. For example, the urineof a wolf includes a mercaptan, and distribution of microbeads fromwhich this mercaptan is gradually released to define a territory willdiscourage deer from entering that territory. Other active materialsuseful in discouraging approach of animals include essences of garlic,putrescent eggs and capsaicin.

[0045] Other active compounds that can be included in the microbeads ofthe invention include perfumes, fragrances, flavouring agents and thelike.

[0046] Optionally, oil absorbents can be incorporated into the activedroplets. These absorbents can help retain the active droplets withinthe microbeads, resulting in longer lasting formulations. Clays andstarches could also be used for this purpose.

[0047] The concentration of active material in the microbeads of theinvention should be at a level such that the matrix forming material canstill provide a strong, rupture resistant network and deliver aneffective amount of the active material to the environment to which itis intended. Thus, the active material is preferably present in anamount between about 0.1 wt % to about 60 weight percent (wt %) of thetotal weight of the microbead. More preferably, the amount of activematerial is present in the microbead at between about 0.2 wt % to about40 wt %; and most preferably between about 0.3 wt % to about 20 wt %.

[0048] Microbeads of the invention comprise at least one layer(hereinafter referred to as a “secondary layer”) adjacent to the outersurface of the hydrophilic matrix core. To provide diffusion and releaseof the active into the atmosphere, the secondary layer can be adiscontinuous layer, or alternatively, a continuous layer permeable toliquid (moisture). The secondary layer that is applied onto themicrobead surface can be performed by chemical processes such as ioniccomplexation or alternatively in-situ polymerization which involveshydrogen bonding of the layer to the matrix core. It is preferable thatthe material used to form the secondary layer is chosen such that thepath of diffusion of the active material is altered to provide extendedrelease of the active. Suitable materials that can be used for thesecondary layer include hydrophilic, hydrophobic, inorganic or organicmaterials or combinations thereof. Preferably, the secondary layer isbiocompatible and easily biodegradeable in the environment.

[0049] In a preferred aspect, the secondary layer can be ionicallycomplexed with the outer surface of the hydrophilic matrix core.Advantageously, an ionically complexed layer provides a differentpermeability and diffusion profile of the active through the secondarylayer, than that of a secondary layer that is covalently bonded to amatrix core. The permeability and diffusion of the actives delivered bythe compositions and methods of the invention provide extended releaseperiods.

[0050] Formation of the secondary layer by ionic complexation isachieved by binding opposing charged groups (i.e. negatively-chargedgroups and positively-charged groups) of the matrix core materials andthe secondary layer. Thus, the selection of the material to form thesecondary layer depends on the surface charge of the hydrophilic matrixcore. If the hydrophilic matrix core is comprised of a negativelycharged hydrophilic material, then the counter charged material shouldbe a positively-charged material, and vice-versa.

[0051] Negatively charged groups suitable for use in the invention,include for example, hydroxyl, carboxyl, sulphate, and phosphate groups.Preferred biocompatible negatively-charged hydrophilic materialsinclude, for example a polysaccharide. Suitable polysaccharides include,for example, an alginate, a carrageenan, in particularkappa-carrageenan, a gelable pectin, in particular a low methoyxylpectin, agar, gellan gum, or combinations thereof.

[0052] Positively-charged hydrophilic materials suitable for use in theinvention include, for example, proteins, polylysines, polypeptide,polyamino acids, polysaccharide bearing amino groups such as chitosanand carboxymethyl cellulose, aliphatics, alicyclic or aromatic organicsubstances bearing several primary or secondary amino groups, such asethylenediamine, hexamethylenediamine, piperazine, phenylenediamine,polyethyleneimine, poly(hexamethylene co-guanidine), or poly(methyleneco-guanidine), or combinations thereof. Of these, chitosan andco-guanidine-containing compounds are particularly preferred. Chitosan,obtained by the deacetylation of chitin, is an amino-polysaccharide anda biopolymer widely distributed in nature. Chitosan is a linearpolysaccharide composed of β-1,4 linked D-glucosamine residues. Innature, the polymer is partially acetylated, and it includes a widerange of polymers corresponding to various proportions of D-glucosamineand N-acetyl-glucosamine residues. The properties of chitosan insolution depend on molecular weight, the degree of deacetylation, pH andionic strength.

[0053] The ionic complexation reaction generally requires an aqueoussolvent. The concentration of the solute (acid or alkaline) ispreferably about 0.01 wt % to about 10 wt %, more preferably about 0.05wt % to about 4 wt %. The solvent is preferably chosen, and its pHadjusted, to avoid precipiation yet ensure satisfactory complexation ofthe counter-charges materials. For example, in a preferred embodimentwhere chitosan solution is used to complex with an alginate, the pH ispreferably between about 1.0 and 6.0, more preferably between about 5.0and 6.0.

[0054] The concentration of the secondary layer forming material ispreferably about 0.01 wt % to about 10.0 wt %, more preferably about0.02 wt % to 4.0 wt % based on the total solution weight.

[0055] In another preferred aspect, the secondary layer can be adjacentto and hydrogen bonded to the outer surface of the hydrophilic matrixcore. This method is performed in-situ, where the secondary layer isdeposited onto the surface of the hydrophilic matrix core.Alternatively, the in situ formation of a secondary layer may be formedby a reaction between a water-immiscible polyisocyanate and awater-miscible polyfunctional amine. The polyisocyanate may be dispersedwithin the hydrogel forming emulsion mixture or dissolved in or withinthe active droplet. Layers formed by the in situ methods can becontinuous and preferably permeable. Suitable materials for use in thein-situ method include for example, polyurea, polyurethane, orpolyureamethylene urea.

[0056] The polyisocyanate may be aromatic or aliphatic and may containtwo, three or more isocyanate groups. Examples of aromaticpolyisocyanates include 2,4- and 2,6-toluene diisocyanate, naphthalenediisocyanate, diphenylmethane diisocyanate and triphenylmethane-p, p′,p″-trityl triisocyanate.

[0057] Aliphatic polyisocyanates may optionally be selected fromaliphatic polyisocyanates containing two isocyanate functionalities,three isocyanate functionalities, or more than three isocyanatefunctionalities, or mixtures of these polyisocyanates. Preferably, thealiphatic polyisocyanate contains 5 to 30 carbons. More preferably, thealiphatic polyisocyanate comprise one or more cycloalkyl moieties.Examples of preferred isocyanates includedicyclohexylmethane-4,4′-diisocyanate; hexamethylene 1,6-diisocyanate;isophorone diisocyanate; trimethyl-hexamethylene diisocyanate; trimer ofhexamethylene 1,6-diisocyanate; trimer of isophorone diisocyanate;1,4-cyclohexane diisocyanate; 1,4-(dimethylisocyanato) cyclohexane;biuret of hexamethylene diisocyanate; urea of hexamethylenediisocyanate; trimethylenediisocyanate; propylene-1,2-diisocyanate; andbutylene-1,2-diisocyanate. Mixtures of polyisocyanates can be used.

[0058] Particularly preferred polyisocyanates are polymethylenepolyphenylisocyanates of formula

[0059] wherein n is 2 to 4. These compounds are available under thetrade-mark Mondur-MRS. The mole equivalent ratio of total primary aminefunctionality to isocyanate functionality in the system is preferablyabout 0.8:1 to 1:1.2, and more preferably about 1:1.1.

[0060] The polyfunctional amine, in the amount used, is preferablyfreely soluble in the water present in the reaction mixture.

[0061] The polyfunctional compound containing amine and/or hydroxyfunctional groups may contain at least two functional groups selectedfrom primary amine, secondary amine and hydroxy groups. Examples ofsuitable compounds include ethylene diamine, diethylene triamine andcompounds of the general formula

[0062] wherein m takes a value from 1 to 8, and each R is independentlyhydrogen or methyl. Also useful are compounds whose structure is similarto the above formula, but which have one or more oxygen atoms present inether linkages between carbon atoms. It is preferred that R is hydrogen,especially at the terminal amino groups. Aromatic diamines, for exampletoluene diamine, can be used. Mixtures of polyfunctional compounds canbe used. Tetraethylene pentamine (TEPA) and pentamethylene hexamine areparticularly preferred.

[0063] A suitable amine for use in this invention is trimethylamine, atertiary amine. This compound, and its C₂, C₃ and C₄ homologues can beused in the microbeads of the invention. Other suitable tertiary aminesinclude those containing a mixture of alkyl groups, for instancemethyldiethylamine. The tertiary amine can contain more than onetertiary amine moiety. It may also contain other functional groupsprovided that those other functional groups do not interfere with therequired reaction, or the functional groups participate beneficially inthe required reaction. As an example of a functional group that does notinterfere there is mentioned an ether group. As examples of groups thatparticipate beneficially there are mentioned primary and secondary aminegroups, which will form urea moieties with isocyanate groups, andhydroxyl groups, which will form urethane moieties with isocyanategroups. Examples of suitable tertiary amines include compounds of thefollowing structures:

[0064] N[CH₂(CH₂)_(n)CH₃]₃, where n is 0, 1, 2 or 3

[0065] Of the tertiary amines triethylamine (TEA) is preferred.

[0066] In another aspect of the in situ formation of the secondarylayer, a water-insoluble non-thermoplastic synthetic resin may be used.Polymerization of the resin generally requires a pre-polymer.Prepolymers suitable to the present invention are partially etherifiedurea-formaldehyde prepolymers with a high solubility in the organicphase and low solubility in water. In its non-etherified form, theprepolymer contains a large number of methylol groups, —CH₂OH, in itsmolecular structure. Etherification is the replacement of the hydroxylhydrogens with alkyl groups; and is preferably achieved by condensationof the prepolymer with an alcohol. Complete etherification is preferablyavoided, however, since hydroxyl groups are needed for the in situself-condensation polymerization, which occurs in the layer formingstep. The secondary layer of this invention may comprise a water-solubleurea resin where at least one of the prepolymers is a mixture offormaldehyde and at least one compound selected from the groupconsisting of urea, melamine and thiourea.

[0067] The microbeads of the present invention can be placed intosuspension in aqueous or solvent-based solutions. For environmental andbiologically-friendly reasons, it is preferred that aqueous suspensionsbe used. Suspension aids are preferably included in the suspensionformulations to ensure the microbeads remain suspended in solution.

[0068] Preferably, the suspension solution is substantially free ofmonovalent cations, such as sodium, to avoid degradation or breakdown ofthe secondary layer or the hydrogel matrix. In a preferred aspect, aconcentration of approximately 50 millimolar of a crosslinker such ascalcium chloride is maintained in a stored solution comprising themicrobeads of the invention.

[0069] Optionally, adhesive material can be included in the compositionsof the invention. The adhesive material can be provided in variousforms, such as for example, latex or a tacky microspheres. Adherentproperties imparted to the hydrogel microbeads should result in themicrobeads being able to still retain their suspended state and minimizeaggregation or coagulation in the aqueous suspension. Furthermore, anyadhesive material used to impart adherent properties should not affectthe integrity of the particles; it should not dissolve or weaken themicrobeads.

[0070] A suitable adhesive material that may be included in thecompositions of the invention is adhesive latex. The adhesive latex maybe any suitable water-dispersible adhesive available in the art. In theagricultural business, such latex compositions are often called stickersor spreaders. Stickers are used to help non-encapsulated agriculturechemicals adhere to plants. Spreaders are used to help dispersenon-encapsulated agriculture chemicals on application. Preferredadhesives are acrylate-based adhesives. One suitable latex is availablefrom Rohm & Haas under the trade-mark Companion. Another is availablefrom Deerpoint Industries under the trade-mark DPI S-100 (a proprietarysticker/spreader). Examples of such adhesives are polymers made from the“soft” monomers such as n-butyl acrylate, isooctyl acrylate, or thelike, or copolymers made from a soft component, such as isobutylene,n-butyl acrylate, isooctyl acrylate, ethyl hexyl acrylate, or the like;and a polar monomer such as acrylic acid, acrylonitrile, acrylamide,methacrylic acid, methyl methacrylate or the like. Non-sphericalpolyacrylate adhesives are commercially available, for example, as theRohm and Haas RhoplexTM line of adhesives. Preferably, the non-sphericalpolyacrylate adhesive is present in an amount of about 10-35% by weightof the total suspension.

[0071] Tacky microspheres of adhesive may alternatively be used to helpadhere the hydrogel microbeads of the invention to an intendedsubstrate. The tacky microspheres have sufficient adhesive properties toprovide the desired adhesive function, yet there is no danger ofcompletely coating the microbead which may lead to potentiallyinhibiting the release characteristics of the microbead. The combinationof microbeads and tacky microspheres may be applied without the need tomodify the orifices of conventional sprayers with minimal clogging orplugging problems. Furthermore, the incorporation of tacky (adhesive)microspheres to the (formulation) suspension of microbeads allows themicrobeads' surfaces to become tacky. The beads can therefore stick tointended surfaces, such as, foliage and branches, for example. Theadhesive microspheres, especially if they are hollow, may also absorbsome of the active material into its own body, thus providing a secondmechanism of release of the active material. This could result in anoverall alteration, preferably an enhancement, of the release profile.

[0072] Preferably, the adhesive material is an acrylate- ormethacrylate-based adhesive system comprising infusible, solventdispersible, solvent insoluble, inherently tacky, elastomeric copolymermicrospheres as disclosed in U.S. Pat. No. 3,691,140. Alternatively,this adhesive composition may comprise hollow, polymer, acrylate,infusible, inherently tacky, solvent insoluble, solvent dispersible,elastomeric pressure-sensitive adhesive microspheres as disclosed inU.S. Pat. No. 5,045,569. Other suitable adhesives are the tackymicrospheres having pendant hydrophilic polymeric or oligomeric moietiesthat are disclosed in U.S. Pat. No. 5,508,313.

[0073] Alternatively, the adhesive comprises between about 60-100% byweight of hollow, polymeric, acrylate, inherently tacky, infusible,solvent-insoluble, solvent dispersible, elastomeric pressure-sensitiveadhesive microspheres having a diameter of at least 1 micrometer, andbetween about 0-40% by weight of a non-spherical polyacrylate adhesive.The hollow microspheres are made in accordance with the teaching ofEuropean Patent Application 371,635.

[0074] The compositions of the present invention may also include one ormore adjuvants including, for example, gelling aids, preservatives,dyes, humectants, fixatives, emulsifiers, extenders, and freeze/thawstabilizers such as polyhydric alcohols and their esters. Thesematerials are present in an amount effective to achieve their extendedfunction, generally less than about 5% typically less than 2%, by weightof the composition.

[0075] Incorporation of a light stabilizer can be included in themicrobeads of the invention. Suitable light stabilizers include thetertiary phenylene diamine compounds disclosed in Canadian Patent No.1,179,682, the disclosure of which is incorporated by reference. Thelight stabilizer can be incorporated by dissolving it, with the active,in a water-immiscible solvent. Alternatively, a light stabilizer can beincorporated in the microbeads as taught in Canadian Patent No.1,044,134, the disclosure of which is also incorporated by reference.

[0076] The process of making the microbeads of the invention, preferablycomprises, initially, the formation of a microemulsion and thedispersion of the active material in the hydrogel material. Themicroemulsion is then mechanically atomized to create substantiallyspherical droplets which are subsequently gelled (hardened) to form ahydrogel microbead having an active material dispersed therein.

[0077] In a preferred method of making the microbeads of the invention,an emulsion of an oil active within a water soluble solution comprisinga hydrogel is first formed. This emulsion is then followed by amechanical microbead forming step that can be performed by, for example,spray method or emulsification. The droplets are then hardened or curedeither by chemical means (i.e., polymer cross-linking) or bynon-chemical means (i.e., temperature, pH, pressure). The resultingmicrobead is a hydrogel microbead, having greater than about 30% waterinitially, and the active would be finely dispersed and entrained withinthe water-polymer matrix. The microbeads tend to be more spherical inshape when the spray method is used, as compared to the emulsificationmethod. The size of the microbeads is generally governed by theintrinsic properties of the emulsion solution, the feed rate and thecoaxial airflow rate.

[0078] The droplets which are atomized can then be allowed to free-falldirectly into a reacting bath. The reacting bath cures or sets thehydrogels so that they solidify. Reaction bath curing can be achievedthrough chemical or non-chemical means. For the case of sodiumalginates, calcium ions are used to cross-link the polymer chains. Apreferred crosslinker is calcium chloride.

[0079] The emulsification method is another technique that can be usedfor producing hydrogel microbeads. In selecting the continuous phasematerial, it is preferable that it be immiscible with both the aqueouspolymer and oil active.

[0080] The matrix-forming material preferably has a range ofconcentrations usable in practicing the invention. The concentrationshould be chosen to optimize ease of handling, gelling time, thestrength of the hydrogel microbead around the active material droplets.For example, a sodium alginate solution can preferably be prepared in aconcentration of about 1 to about 10% (w/v) in water, more preferablyabout 1.5 to about 5% and most preferably from about 1 to 3%. However,if the hydrogel agent concentration is too great, the solution may be soviscous as to hinder the formation of spherical microbeads.

[0081] Alternatively, hydrogel microbeads of the invention can beformed, for example, by adding the matrix forming material solutiondrop-wise to a selected crosslinker. For example, a method can be usedwhereby droplet formation and crosslinker addition is completed as a onestep process by a vibrating nozzle which ejects a hydrogel droplet fromone source and coats the droplet with a crosslinker from another. U.S.Pat. No. 4,701,326 teaches use of this method.

[0082] In the preferred aspect where alginates are used to immobilize anactive material, a crosslinker is preferably made up in solution at aconcentration of 1 to 1000 millimolar, more preferably 20 to 500millimolar and most preferably from 50 to 100 millimolar. Theconcentration ranges may have to be adjusted, depending on the nature ofa crosslinker and matrix-forming material.

[0083] The microbeads containing matrix material and active material canbe treated with the crosslinker solution by soaking, spraying, dipping,pouring or any of sever other methods which will deposit an amount ofthe complexing agent on the droplet. When soaking, the time in solutionmay be from 1 second to 24 hours, preferably 1 minute to 1 hour, andmore preferably from 10 to 30 minutes.

[0084] The temperature for hydrogel microbead formation is preferablychosen as to avoid damage or alteration to the active material. Forexample, in the preferred aspect where alginates are utilized, thetemperature is preferably in the range of about 1° C. to about 70° C.;more preferably between about 10° C. to about 40° C., and mostpreferably between about 15° C. to about 30° C.

[0085] Forming the secondary layer of the microbead may be accomplishedin various methods. In one aspect, both the secondary layer and thehydrophilic matrix core can be produced substantially simultaneously. Inthis process, the ionically complexed layer is formed while thecrosslinker diffuses into the matrix-forming material to form (gel) thematrix core.

[0086] In a preferred method utilizing ionic complexation to form thesecondary layer, the active material is emulsified and entrained intothe matrix-forming material with the aid of surfactants. The intactbeads are then placed into an ionically complexing solution containingopposing charges (either positively or negatively charges), depending onthe selection of the hydrophilic matrix forming material for a specifiedperiod of time.

[0087] The reaction time or the length of incubation time of thesecondary layer forming material and the matrix forming material shouldbe sufficient to complex to the hydrogel bead. Preferably, the reactiontime is between 5 min to 3 hours, preferably between 5 min and 1 hour,and even more preferably is 30 min.

[0088] In a preferred method where in situ polymerized polyurea (PU)membranes are formed as the secondary layer, the polyisocyantes arefirst dispersed within the matrix forming material and/or along with theactive material. The microbeads can then be formed in a crosslinkingsolution, where the secondary layer is formed substantiallysimultaneously as the matrix core with active droplets entrainedtherein.

[0089] In another preferred method where in situ polymerizedpolymethylene urea membranes (PMU) are formed on hydrogel microbeads,the matrix core with active droplets entrained therein is formed priorto forming the secondary layer. The secondary layer is then preferablyformed by providing an aqueous solution of a water-soluble,low-molecular weight urea-aldehyde precondensate comprisingpredominantly low molecular weight reaction products of urea, melamineor thiourea and formaldehyde and adding acid thereto in amount toprovide a pH for the dispersion in the range of about 1 to 6.0 and morepractically about 1.0 to 3, thereby promoting acid catalysis of theprecondensate. Polymerization of the precondensate to a water-insolubleurea-formaldehyde polymer can be continued by agitation within apreferable temperature range of about 20 to about 90° C. for at leastabout one hour. The polymerized layer can then be neutralized usingsodium hydroxide.

[0090] Prior to adding the microbeads a suspending solution, themicrobeads are preferably washed and filtered using, for example, aBuchner type funnel.

[0091] Surfactants can be used in the process of forming the microbeads.The incorporation of different surfactants will offer different types ofmicroemulsion drop sizes of the active within the hydrogel as well asdictate the amount of free oil lost in the reacting bath solution. Apreferred surfactant has a high critical micelle concentration, such asfor example, a product available under the product designation DISPONILSUS IC 875 (CMC˜1%)., available from Henkel (Ambler, Pa.).

[0092] Particularly preferred surfactants are nonionic. Examples ofsuitable surfactants include polyvinylpyrrolidone (PVP) andpoly(ethoxy)nonylphenol. PVP is usable and available at variousmolecular weights in the range of from about 20,000 to about 90,000. PVPhaving a molecular weight of about 40,000 is preferred.Poly(ethoxy)nonylphenols are commercially available under the tradedesignation IGEPAL from Rhone-Poulenc (Cranbury, N.J.), with variousmolecular weights depending on the length of the ethoxy chain.Poly(ethoxy)nonylphenols having the formula:

[0093] where n has an average value from about 9 to about 13 can beused. A preferred poly(ethoxy)nonylphenols is available commerciallyunder the product name IGEPAL 630, from Rhone-Poulenc (Cranbury,N.J.)—630 is indicative of the approximate molecular weight of thecompound. Other examples of suitable surfactants include polyether blockcopolymers, such as those available under the trade designationsPLURONIC and TETRONIC, both available from BASF (Washington, N.J.),polyoxyethylene adducts of fatty alcohols, such as BRIJ surfactantsavailable from ICI (Wilmington, Del.), and esters of fatty acids, suchas stearates, oleates, and the like. Examples of such fatty acidsinclude sorbitan monostearate, sorbitan monooleate, sorbitansesquioleate, and the like. Examples of the alcohol portions of thefatty esters include glycerol, glucosyl and the like. Fatty esters arecommercially available as surfactants under the trade designationARLACEL C from ICI (Wilmington, Del.) Various properties of thesurfactant, such as for example, chain length, functional groups, andhydrophobic regions, can affect the size of the active droplets formedwithin the microbeads. For example, use of PVP (having a molecularweight of 40,000) tend to result in production of larger sized activedroplets than use of poly(ethoxy)nonylphenols (IGEPAL 630).

[0094] Ionic surfactants can alternatively be used in the processes ofthe invention. Examples of suitable ionic surfactants partiallyneutralized salts of polyacrylic acids such as sodium or potassiumpolyacrylate or sodium or potassium polymethacrylate.

[0095] The active material entrained in the microbeads of the inventionare released gradually over time. While not being bound by this theory,it is believed that a mechanism of release of the active in themicrobeads of the invention involves water evaporation from the matrixcore and then diffusion of active through the secondary layer. Inanother aspect, the active may be released by entrainment with thehydrogel matrix as the water evaporates, in addition to release bydiffusion through the secondary layer. Where multiple layers areoptionally included in the microbeads of the invention, the activepreferably diffuses though each layer.

[0096] In preferred applications, these hydrogel microbeads would besprayed followed by water evaporation within the gel. As the hydrogelbead dehydrates, the matrix shrinks in size and releases its active withtime. The degree of shrinkage of the microbead from its original size,depending on the components used in the formulation. Preferably, themicrobeads shrink about 10 to about 90% from its original size, morepreferably from about 40 to about 80%, and most preferably from about50% to about 70%.

[0097] Active release from the microbeads of the invention hassurprisingly been found to be controllable by controlling the humidity(and dryness) of the environment in which the microbeads are in.Advantageously, the microbead, upon re-exposure to humidity, can swelland rehydrate itself by absorbing water. Re-exposure to humidity can beperformed in various ways. For example the microbeads' surfaces can becontacted directly with water or other aqueous solutions. Inagricultural applications where pheronomes are used as the activematerial, a farmer or caretake can irrigate the plants and foliage tore-hydrate the hydrogel microbeads. Alternatively, the humidity of theenvironment or ambient air in which the microbeads are located in can beincreased by entraining air droplets in the air. Thus, the microbeadscan be “re-activiated” by re-hydration, thereby selectively controllingthe release times of the active material.

[0098] It is contemplated that in the preferred embodiment where themicrobead comprises a secondary layer ionically complexed to the matrixcore surface, swell rates or rehydration effects may result in a furtheralteration of the release profile of the active. This may be due to thesecondary layer having a different absorption rate than that of thehydrophilic matrix core. Advantageously, this can provide extendedrelease profiles of the active to a desired environment.

[0099] The microbeads of the invention can be delivered to an intendedsubstrate by various methods. In the preferred embodiment where theactive material is a pheromone, delivery of the microbeads will dependon various factors, such as for example, the size of release coveragedesired. For small concentrated areas, the microbeads can be impregnatedinto hollow fibres, plastic laminate flakes or twist-ties and thenphysically attaching the fibres or ties to plants to be protected frominsect infestation. For larger areas, spraying (aerially or byback-pack) may be the better option.

[0100] All patents cited in this specficiation are hereby incorporatedby reference.

[0101] The following examples are provided to illustrate, but not limit,the scope of the invention. Unless otherwise specified, all parts andpercentages are by weight.

EXAMPLES

[0102] The following list of materials were used in the Examples. Listedadjacent to each material is the manufacturer and/or supplier from whichthe materials were obtained. 3M HFE 7100 3M Co. (St. Paul, MN) CarvoneBedoukian (Danbury, CT) Disponil SUS IC 875 Henkel (Ambler, PA) Drakeol34 Penreco (Karns City, PA) E,E-8,10-C12 alcohol Shin-Etsu Chemical Co.,Ltd. (Tokyo, Japan) Igepal C0-630 Rhone-Poulenc (Cranbury, New Jersey)Menthone Berjé (Bloomfield, NJ) Paraffin Wax Aldrich Chemical Co.(Milwaukee, WI) Sodium alginate SKW (Lannilis, France) Solvent 100 ShellChemical Co. (Bayway, NJ) Starch Aldrich Chemical Co. (Milwaukee, WS)Tixogel EZ100 Süd-Chemie Rheologicals (Louisville, KY) Z11-C14 acetateShin-Etsu Chemical Co., Ltd. (Tokyo, Japan)

TEST METHODS

[0103] To evaluate the physical performance of microbeads of theinvention, two parameters were measured: (1) air concentrations ofpheromone released from the microbead formulation and (2) the amount ofactive remaining (i.e., residual concentration) in the microbead overtime.

[0104] Air Concentration Determination

[0105] A known amount of beads (10 microbeads) were recovered and placedin a constant airflow chamber of 100 mL/min (˜23-24° C. temperature).The effluent air stream from the chambers was analyzed for activeconcentration using solid phase microextraction (SPME) (Supelco,Bellefonte, Pa.) and gas chromatography (GC) (Varian ChromatographySystems, Walnut Creek, Calif.) over a period of weeks to evaluate theperformance of the hydrogel microbeads.

[0106] To calculate the Release Rate of an active, the Air Concentrationis multiplied by the Air Flow rate.

[0107] Residual Concentration Determination

[0108] Formulations were filtered using a Buchner type vacuum funnel,washed with room temperature distilled water and dried in a fumehood atroom temperature for 24 hours. Fifty milligrams of the dried formulationwere put on tinfoil squares as application substrates. After therequired exposure time, the microbeads were subjected to extraction forat least 24 hours with 4 mL of dichloromethane to determine the residuallevel of active still remaining in the formulation. Each collectedsample was then analyzed by gas chromatography.

Example 1 Formation of Pheromone Entrapped Hydrogel Microbeads

[0109] For each of the Samples A-J (shown in Table 1), a sodium alginatesolution was initially prepared by dissolving a preweighed amount ofalginate into a known volume of distilled water. The solution was mixedthoroughly to solubilize the polymer and was deaerated for removal ofentrained air bubbles. In a separate 250 mL vessel, the active andsurfactant was added and mixed at a speed of about 2000 RPM using amarine type impeller (3.81 cm diameter). To the mixture, the alginatesolution was gradually added to form the microemulsion. The emulsion washomogenized for about 30 minutes. The emulsion was then atomized intofine particle droplets using a coaxial air nozzle sprayer. The size ofthe particles was determined by the settings on the atomizing device.This involved control of the nozzle head diameters, the feed rate of theemulsion through the nozzle and the airflow which passed along its feedpath (shown in Table 2). For an example, to create fine particles withinthe sprayable range (Sample E), the nozzle feed diameter was 0.508 mm,the coaxial air nozzle was 1.4 mm, the feed pressure was about34.4-110.3 kPa, and the airflow was about 13.8-34.5 kPa. As a result,discrete spherical microbeads were produced with a particle size rangeof 4 to 400 microns.

[0110] Examples A-F demonstrated the ability of this invention toencapsulate oils or pheromones with function groups of ketones,alcohols, and acetates. All the formulations resulted in sphericalintact hydrogel microbeads containing the desired active.

[0111] Examples G-I demonstrated the ability of this invention to absorboils or pheromones with functional groups of ketones, alcohols, andacetates within an absorbent material prior to encapsulation within ahydrogel matrix. All the formulations resulted in spherical intacthydrogel microbeads containing the desired active. TABLE 1 Hydrogelmicrobead formulations Sodium alginate Conc. Active Surfactant Calcium(g/100 Weight Weight Weight conc. Sample mL) (g) Type (g) Type (g) (mM)A 2.0 50.0 Carvone 20.0 Igepal 2.0  50 CO-630 B 2.0 50.0 Carvone 5.0Igepal 1.0  50 CO-630 C 2.0 38.6 E, E-8, 10-C12 1.0 Disponil 1.0  50alcohol/Solvent SUS IC 100 (1:4 by wt) 875 D 2.5 250.0 Menthone 50.0Igepal 5.0  50 CO-630 E 2.5 800.0 Z11-C14 acetate 20.0 Igepal 2.0 1000CO-630 F 2.0 38.6 Z11-C14 acetate 1.0 Disponil 0.4  50 SUS IC 875 G 2.040.0 Z11C14 acetate/ 3.0 n/a  50 starch (1:4 by wt) H 2.5 250.0Menthone/ 56.0 n/a  50 Tixogel EZ100 (8:1 by wt) I 2.5 250.0 Menthone/44.0 n/a  50 parrafin wax (10:1 by wt)

[0112] Hydrogel microbeads were formed using coaxial airflowatomization, using the formulations of Samples A and E. Average particlediameters were measured by evaluating 30-50 microbeads, using astereomicroscope product name STEREOZOOM 7 available from Bausch & Lomb(Brick, N.J.) and a light microscope product LEITZ DIAPLAN availablefrom Ernst Leitz (Wetzlar, West Germany). The nozzle size and settingsvaried respectively to produce different size particles, as shown inTable 2. TABLE 2 Feed Nozzle Coaxial air Mean Diameter Pressure DiameterPressure Diameter Sample (in.) (psi) (in.) (psi) (mm) A 0.020 10 0.046 02.8  0.016 20 0.046 0 1.7  0.020 10 0.046 5 0.9  0.016 20 0.046 5 0.2  E0.020  5 0.055 5 0.094 0.020 16 0.055 2 0.135 0.020 16 0.055 5 0.1260.020 14 0.055 4 0.063

Example 2 Ionic Complexation to Form Secondary Layer Example 2A 2 StepProcess

[0113] The procedure outlined in EXAMPLE 1 was adopted, where Sample Ewas used, with the variation that a polymer forming solution was usedfirst to crosslink the emulsion droplet on the outside peripherial. In avessel, a solution of chitosan (Seacure 143, Pronova Biopolymer,Washington) containing 5% glacial acetic acid was prepared by mixing atroom temperature. The solution pH was adjusted to about 5.6 using sodiumhydroxide. The method of microbead preparation utilizing coaxial airatomization was also adopted using protocol demonstrated in EXAMPLE 1.As an example, the nozzle feed diameter was 0.020 inches, the coaxialair nozzle diameter was 0.055 inches, the feed pressure was about 10psi, and the airflow was set to 0 psi. After the microbeads were formed,they were soaked in the forming solution for about 3-4 hours. Tosolidify the membrane bound pheromone droplets, 11 g of calcium chloridecrystals were added to the suspension. The microbeads were then gelledfor 3-4 hours, filtered and washed with water. As a result of thefollowing example, discrete spherical menthone immobilized hydrogelmicrobeads were produced with an average particle size of about 2.5millimeters.

Example 2B 1 Step Process

[0114] The procedure outlined in EXAMPLE 1 was adopted, where SAMPLE Awas used, in addition to a polymer forming solution along with thecalcium chloride. In a vessel, a solution of chitosan (Seacure 143,Pronova Biopolymer, Washington) containing 1% glacial acetic acid and 50millimolar calcium chloride was prepared by mixing at room temperature.The solution pH was adjusted to about 5.6 using sodium hydroxide. Themethod of microbead preparation utilizing coaxial air atomization wasalso adopted using protocol demonstrated in EXAMPLE 1. The nozzle feeddiameter was 0.020 inches, the coaxial air nozzle diameter was 0.055inches, the feed pressure was about 10 psi, and the airflow was set to 0psi. As a result of the following example, discrete spherical carvoneimmobilized hydrogel microbeads were produced with an average particlesize of about 3.2 millimeters.

Example 3 In-situ Polymerization Preparation of the Prepolymer

[0115] A 1 L jacketed reactor set to 71° C. was charged with 326.0 gformaldehyde (Hoechst-Celanese, Rock Hill, S.C.), 121.6 g urea (ArcadianCorporation, Memphis, Tenn.) and 1.14 g potassium tetraboratetetrahydrate (Aldrich Chemical Co., Milwaukee, Wis.). The solution wasmixed for 2.5 hours at 350 RPM using a six blade turbine. Dilution water(552.4 g) was then added and mixed well before bottling and storing atroom temperature.

Example 3A

[0116] The procedure outline in EXAMPLE 1 was adopted, where Sample Ewas used to produce discrete menthone immobilized in microbeads of about1 millimeter in diameter. Filtered and water washed microbeads wereplaced into a 35° C. jacketed reactor charged with distilled, roomtemperature water (43.86 g) and the prepolymer solution (101.54 g). Thesuspension was then mixed at about 100 RPM using a six blade turbine for5 minutes. Gradually, the pH was was adjusted from an initial 8.5 to afinal 2.8 using concentrated sulfuric acid (1.2N) at an approximate rateof 0.08 pH units/min. The reaction was stirred at 100 RPM for 30minutes, before lowering the pH to 2.1 and temperature to 25° C. Thereaction was stirred for a further 1 hour, then the temperature wasincreased to 60° C. over 15 minutes, and the mixture held for a final 1hour. The reaction mixture was cooled to room temperature andneutralized with ammonium hydroxide. The microbeads were filtered andwashed several times with water. The resulting microbeads were discreteand possessed a rigid, hard coating.

Example 3B

[0117] The procedure outlined in EXAMPLE 3A was adopted and followedexcept that the microbeads used were chitosan layered menthone hydrogelmicrobeads obtained from EXAMPLE 2A. The resulting microbeads werediscrete and possessed a secondary layer.

Example 3C

[0118] The procedure outline in EXAMPLE 3A was adopted and followedexcept that the microbeads used were carvone hydrogel microbeadsobtained from Sample B. The resulting microbeads were discrete andpossessed a secondary layer.

Example 3D

[0119] The procedure outline in EXAMPLE 3A was adopted and followedexcept that the microbeads used were menthone absorbed in clay (TixogelEZ 100, Süd-Chemie Rheologicals, Louisville, Ky.) calcium alginatehydrogels obtained from Sample I. The resulting microbeads were discreteand possessed a secondary layer.

Example 3E

[0120] The procedure outline in EXAMPLE 3A was adopted and followedexcept that the microbeads used were menthone absorbed in wax (ParaffinWax, Aldrich) calcium alginate hydrogels obtained from Sample J. Theresulting microbeads were discrete and possessed a secondary layer.

Example 4

[0121] Following the test methods described above for Air Concentration,known batches from Sample A and Example 2B were evaluated over aduration of at least 7 seeks while Sample B and Example 3C wereevaluated for 5 days. Tables 3 provides the release rate analysis. AirConcentration Determination analysis showed a burst of active (carvone)in the air during the first day followed by a gradual decrease with timefor all formulations. In the initial portion of the total releaseperiod, the release rate for the microbeads comprising a secondary layerwas observed to be significantly lower than that of non-layeredmicrobeads. Subsequently, the longevity of the release is extendedsignificantly as a result of forming an ionically complexed layer onhydrogel microbeads. Similarly, lower release rates were observed for insitu polymerized layers at the initial. This, in turn, increases thelongevity of the release. TABLE 3 Release rate in air (ng/min per mgcarvone) Time Sample A Example 2B Sample B Sample 3C (days) No 2^(nd)layer w/layer No 2^(nd) layer w/layer 0 165.9 144.8 601.6 72.2 0.05556.8 123.0 554.2 25.3 0.08 941.2 126.3 — — 0.12 877.5 248.9 — — 0.15854.2 467.8 498.6 15.3 1 — 141.9 — — 2 43.3 118.7 2.1 1.1 5 0.001 36.21.0 0.5 8 — 0.177 — — 10 0.001 0.089 — — 13 0.001 — — — 15 — 0.026 — —18 — 0.016 — — 20 — 0.017 — — 25 — 0.011 — — 47 — 0.007 — — 61 — 0.004 ——

What is claimed is:
 1. A microbead comprising a hydrophilic matrix corehaving a plurality of active material droplets entrained in said matrixcore, said core having an outer surface, and a secondary layer adjacentand ionically complexed to said outer surface.
 2. The microbead of claim1 wherein said secondary layer is discontinuous.
 3. The microbead ofclaim 1 wherein said secondary layer is a continuous layer permeable toliquid.
 4. The microbead of claim 1 wherein said secondary layercomprises a material selected from the group consisting of chitosan,poly(hexamethylene co-guanidine), poly(methylene co-guanidine),polyethyleneimine and combinations thereof.
 5. The microbead of claim 1wherein said secondary layer is hydrophobic.
 6. The microbead of claim 1wherein said hydrophilic matrix core is made from a polysaccharide. 7.The microbead of claim 8 wherein said polysaccharide is selected fromthe group consisting of alginate, chitosans, carrageenan, gum and agar.8. The microbead of claim 1 wherein said active material is selectedfrom the group consisting of pheromone, mercaptan-containing compound,herbicide, pesticide, and pharmaceutical material.
 9. The microbead ofclaim 1 wherein said microbead has an average diameter of about 1micrometers (μm) to about 1000 μm.
 10. The microbead of claim 1 whereinsaid microbead has an average diameter of about 1 μm to about 500 μm.11. The microbead of claim 1, wherein said microbead further comprises asurfactant.
 12. The microbead of claim 1 wherein said microbead furthercomprises an oil absorbent.
 13. The microbead of claim 1 wherein saidactive material is present in an amount between about 0.1 wt % to about60 wt % of the total weight of said microbead.
 14. The microbead ofclaim 1 wherein said active material is present in an amount betweenabout 0.2 wt % to about 40 wt % of the total weight of said microbead.15. The microbead of claim 1 wherein said active material is present inan amount between about 0.3 wt % to about 20 wt % of the total weight ofsaid microbead.
 16. The microbead of claim 1 wherein said hydrophilicmatrix core is an alginate, said active material is a pheromone, andsaid secondary layer is formed using chitosan or a co-guanidinecontaining compound.
 17. A microbead comprising a hydrophilic matrixcore having a plurality of active material droplets entrained in saidmatrix core, said core having an outer surface, and a secondary layeradjacent and hydrogen bonded to said outer surface.
 18. The microbead ofclaim 17 wherein said secondary layer is discontinuous.
 19. Themicrobead of claim 17 wherein said secondary layer is a continuous layerpermeable to liquid.
 20. The microbead of claim 17 wherein saidsecondary layer is hydrophobic.
 21. The microbead of claim 17 whereinsaid secondary layer comprises a material selected from the groupconsisting of polyurea, polymethylene urea, and polyurethane.
 22. Themicrobead of claim 17 wherein said hydrophilic matrix core is made froma polysaccharide.
 23. The microbead of claim 22 wherein saidpolysaccharide is selected from the group consisting of alginate,chitosans, carrageenan, gum and agar.
 24. The microbead of claim 17wherein said active material is selected from the group consisting ofpheromone, mercaptan-containing compound, herbicide, pesticide, andpharmaceutical material.
 25. The microbead of claim 17 wherein saidmicrobead has an average diameter of about 1 μm to about 1000 μm. 26.The microbead of claim 17 wherein said microbead has an average diameterof about 1 μm to about 500 μm.
 27. The microbead of claim 17 whereinsaid microbead further comprises a surfactant.
 28. The microbead ofclaim 1 wherein said microbead further comprises an oil absorbent. 29.The microbead of claim 17 wherein said active material is present in anamount between about 0.1 wt % to about 60 wt % of the total weight ofsaid microbead.
 30. The microbead of claim 17 wherein said activematerial is present in an amount between about 0.2 wt % to about 40 wt %of the total weight of said microbead.
 31. The microbead of claim 17wherein said active material is present in an amount between about 0.3wt % to about 20 wt % of the total weight of said microbead.
 32. Themicrobead of claim 17 wherein said hydrophilic matrix core is analginate, said active material is a pheromone, and said secondary layeris polyurea.
 33. A sprayable composition comprising a plurality of themicrobeads of claim 1 suspended in a solution.
 34. The composition ofclaim 33 further comprising adhesive material selected from the groupconsisting of hollow tacky adhesive microspheres, solid tacky adhesivemicrospheres, latex, and combinations thereof.
 35. The composition ofclaim 33 wherein said microbeads further comprise an additive selectedfrom the group consisting of preservatives, humectants, stabilizers, UVprotectants, and combinations thereof.
 36. A sprayable compositioncomprising a plurality of the microbeads of claim 17 suspended in asolution.
 37. The composition of claim 36 further comprising adhesivematerial selected from the group consisting of hollow tacky adhesivemicrospheres, solid tacky adhesive microspheres, latex, and combinationsthereof.
 38. The composition of claim 36 wherein said microbeads furthercomprise an additive selected from the group consisting ofpreservatives, humectants, stabilizers, UV protectants, and combinationsthereof.
 39. A method of delivering and releasing active materialcomprising the steps of: a) suspending a plurality of said microbeads ofclaim 1 in a solution; b) delivering said solution comprising saidmicrobeads onto a substrate; and c) allowing said microbeads todehydrate.
 40. The method according to claim 39 further comprising thesteps of: d) exposing said microbeads to humidity; and e) allowing saidmicrobeads to rehydrate.
 41. The method according to claim 39 whereinsaid active material is a pheromone and said hydrophilic matrix core isan alginate.
 42. The method according to claim 40 wherein said step ofexposing said microbeads to humidity is performed by wetting thesurfaces of said microbeads with a solution.
 43. The method according toclaim 40 wherein said step of exposing said microbeads to humidity isperformed by adding moisture to the ambient air.
 44. The methodaccording to claim 40 wherein said steps c) thru e) are repeatedsequentially.
 45. A method of delivering and releasing active materialcomprising the steps of: a) suspending a plurality of said microbeads ofclaim 17 in a solution; b) delivering said solution comprising saidmicrobeads onto a substrate; and c) allowing said microbeads todehydrate.
 46. The method according to claim 45 further comprising thesteps of: d) exposing said microbeads to humidity; and e) allowing saidmicrobeads to rehydrate.
 47. The method according to claim 45 whereinsaid active material is a pheromone and said hydrophilic matrix core isan alginate.
 48. The method according to claim 46 wherein said step ofexposing said microbeads to humidity is performed by wetting thesurfaces of said microbeads with a solution.
 49. The method according toclaim 46 wherein said step of exposing said microbeads to humidity isperformed by adding moisture to the ambient air.
 50. The methodaccording to claim 46 wherein said steps c) thru e) are repeatedsequentially.